The present invention relates generally to catheters and, more particularly, to catheters for irradiating vessels, lumens or cavities of a body, such as cardiovascular tissue to reduce the incidence of restenosis, and to treat other conditions.
Restenosis of an artery or vein after percutaneous transluminal coronary angioplasty (PTCA) or percutaneous transluminal angioplasty (PTA) occurs in about one-third of the procedures, requiring the procedure to be repeated. Various types of drugs or other agents are being investigated for use in preventing restenosis. Heparin, an anticoagulant and inhibitor of arterial smooth muscle proliferation, is one such drug. Dexamethasone may also prevent smooth muscle proliferation. Integralin, which prevents aggregation of platelets, may also be useful. Other anticoagulants and antiproliferative agents are being investigated for efficacy, as well. Such drugs can be delivered before or after the angioplasty procedure. The delivery of lytic agents such as urokinase, streptokinase and recombinant tissue type plasminogen activator (rTPA) to dissolve thrombi in arteries and veins is also being investigated.
Because of blood flow through the artery, drugs delivered to the site of an angioplasty procedure, for example, can be rapidly dissipated and removed from the site before they can be sufficiently absorbed to be effective. Catheters have therefore been developed to directly drive the drug into the desired site through a balloon or to maintain the delivered drug agent proximate the desired site by isolating the region with occlusion balloons. See, for example, U.S. Pat. Nos. 5,087,244, 4,824,436, and 4,636,195, to Wolinsky.
The use of sufficient pressures to drive the drug into the tissue or plaque, however, may damage the arterial wall. Passive delivery into a region isolated by occlusions balloons, on the other hand, is slow and may not enable sufficient absorption of the medication. Passive delivery can be particularly inappropriate for drug delivery in an artery because blood flow can only be occluded in an artery for a limited period of time.
Stents have also been used after angioplasty to prevent an opened blood vessel from closing. The use of stents, however, has only shown a small decrease in the incidence of restenosis. Stents are also difficult to properly position and are expensive.
The use of radiation has also been investigated to reduce restenosis after PTCA or PTA. One technique is Photodynamic Therapy (PDT), wherein photosensitive drugs delivered to the angioplasty site are activated by irradiation with ultraviolet (UV) or visible light.
Another approach was to expose vascular tissue to UV light within a wavelength band of DNA absorption (240-280 nm) by a laser to disable or destroy the DNA of the tissue. This would impair or destroy the ability of the vascular tissue to proliferate. This approach had only limited success, however, because UV light does not penetrate vascular tissue sufficiently to prevent proliferation or migration of smooth muscle tissue.
Beta-irradiation of the vessel after angioplasty with radioactive guide wires or implanted stents is another technique. U.S. Pat. No. 5,199,939 to Dake et al., for example, discloses a catheter with radioactive pellets at its distal end to irradiate the site of an angioplasty procedure to prevent restenosis. The need for a radioactive source in the catheter lab, however, requires protection against radioactive hazards to personnel and costly compliance with regulations. It is also difficult to control the depth of penetration of the radiation by this method.
U.S. Pat. No. 4,143,275 to Mallozzi et al., discloses an x-ray device for delivering radiation to remote locations of the human body such as the interior of the heart. The x-ray radiation is generated by irradiating a target material, such as iron, calcium, chromium, nickel, aluminum, lead, tungsten or gold, by a laser to vaporize the metal. X-ray radiation is emitted from the ionized vapor plasma. The target is located outside the body and the x-rays are directed to a desired location within the body through a hollow guide. The patent discusses use of such a device to produce radiographs, to irradiate tumors or to alter tissue. It is believed, however, that x-ray radiation generated by this method would have photon energy of about 1-2 KeV at best, which is too low to penetrate biological tissue deeper than about 20-30 microns. In addition, the patent does not disclose how to produce a guide which is both flexible enough to be advanced through the cardiovascular system and able to transmit adequate x-ray radiation to an intended site without excessive losses.
U.S. Pat. No. 5,153,900 to Nomikos, et al., discloses a miniaturized low power x-ray source for interstitial insertion for the treatment of tumors. The device comprises a housing with an elongated cylindrical, rigid probe. An anode and cathode are located in the housing and a target is located at the distal end of the probe. The cathode and target must lie along the same axis. Electrons emitted by the cathode, which can be a thermionic emitter or a photocathode, impinge on the target, causing the emission of x-ray radiation. A rigid probe is unsuitable for use in the cardiovascular system.
U.S. Pat. No. 5,428,658 to Oettinger, et al., a continuation of the patent to Nomikos, discussed above, discloses a flexible probe comprising a flexible optical fiber within a metallic tube. The optical fiber has a photoemissive coating at its terminal end. A target is located distal to the terminal end of the optical fiber, within an evacuated shell. The flexible probe is said to enable threading down a pathway, such as the trachea, or around structures, such as nerves or blood vessels. Such a device is not sufficiently flexible for advancement through the cardiovascular system, nor is it believed that such a device can be made small enough to access the site of a PTCA procedure.
U.S. Pat. No. Re 34,421 to Parker, et al. discloses an x-ray microtube comprising a glass tube having a diameter less than one inch, for insertion into the body for treating a tumor. While asserting that the diameter can be as small as xe2x85x9 inch, Parker does not address any of the problems associated with such a small device, such as electrical flashover. It is questionable whether such a device could be made small enough to access the site of a PTCA procedure, and still function. Glass also has too high a coefficient of absorption of x-ray radiation to enable delivery of sufficient x-ray radiation to prevent restenosis in a reasonable period of time. Parker also does not disclose any way to advance its x-ray source through the cardiovascular system, or any other channel of the body.
In accordance with a preferred embodiment of the present invention, an x-ray catheter is disclosed which is small and flexible enough to access an intended site within a vascular system of the body, such as the coronary arteries of the cardiovascular system. The x-ray catheter can operate at the high voltages required for generating x-ray radiation of an effective spectrum for preventing restenosis and treating other conditions. It also has walls highly transmissive to x-ray radiation so that an effective dosage can be delivered in a short period of time.
In accordance with the present invention, a catheter for emitting x-ray radiation is disclosed comprising a flexible catheter shaft having a distal end and an x-ray unit coupled to the distal end. The x-ray unit comprises an anode, a cathode and an insulator, wherein the anode and cathode are coupled to the insulator to define a vacuum chamber. The insulator is preferably pyrolytic boron nitride, which is highly transmissive to x-ray radiation. The cathode is preferably a field emission cathode of graphite, graphite coated with titanium carbide, or other carbides. The cathode can also comprise silicon and the x-ray unit can include a grid. The cathode can be a ferroelectric material, as well. The anode is preferably tungsten. The catheter shaft is preferably a coaxial cable. A guide wire may be provided extending through the catheter shaft, partially through the catheter shaft or partially through the x-ray unit, in a rapid exchange configuration. The catheter further preferably comprises a means for centering the x-ray unit within a lumen.
In accordance with another embodiment of the invention, an x-ray catheter is disclosed comprising a flexible catheter shaft for being advanced through lumens of a vascular system.
Another embodiment of the present invention comprises an x-ray generating unit having a diameter less than about 4 mm.
Yet another embodiment of the present invention comprises a catheter shaft, an x-ray generating unit and means for centering the x-ray generating unit within the lumen.
A method is also disclosed in accordance with the present invention for preventing restenosis of a lumen or treating other conditions, comprising advancing an x-ray catheter through a lumen to a first location adjacent an intended site of the lumen, wherein the x-ray catheter comprises a flexible catheter shaft with a distal end and an x-ray generating unit coupled to the distal end. The x-ray generating unit comprises an anode, a cathode and an insulator, wherein the anode and cathode are coupled to the insulator to define a vacuum chamber. The method further comprises causing the emission of an effective dose of x-ray radiation and removing the catheter. The catheter can be inserted after conducting an angioplasty procedure. The catheter can be advanced over a guide wire and through a guide catheter, or through an exchange tube.